RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients will respond to treatment with erlotinib.

PURPOSE: This clinical trial is studying how well erlotinib works when given before surgery in treating patients with head and neck cancer that can be removed by surgery.

Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:

Identify tissue biomarkers of EGFR activation and inhibition for which initial values and changes after treatment with erlotinib hydrochloride would best correlate with the objective response of the tumor measured clinically and radiologically [ Designated as safety issue: No ]

Secondary Outcome Measures:

Objective response [ Designated as safety issue: No ]

Tumor cell metabolic response measured by PET scan at 4-6 days after beginning of treatment and correlation with tumor response evaluated at the end of treatment by CT scan, PET scan, and direct tumor measurements [ Designated as safety issue: No ]

Role of PET/CT scan in evaluating response to short-term treatment with erlotinib hydrochloride and comparison with the same response evaluation performed by CT scan [ Designated as safety issue: No ]

Incidence of risk factors for relapse [ Designated as safety issue: No ]

Any treatment-induced delay of the established date for definitive surgical treatment [ Designated as safety issue: Yes ]

Enrollment:

24

Study Start Date:

March 2008

Primary Completion Date:

October 2014 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Identify tissue biomarkers (primarily the level of phosphorylation of individual C-terminal EGFR tyrosine sites, measured by nano-LC-MS/MS and markers of main downstream pathways activation such as P-AKT and P-ERK, measured by nano-LC-MS/MS and by more clinically standardized IHC) that best associate with response to neoadjuvant erlotinib hydrochloride treatment in patients with resectable squamous cell carcinoma of the head and neck (HNSCC).

Determine the best correlations between levels and changes of different individual biomarkers (e.g., levels of C-terminal EGFR phosphorylation and recruited adaptors and markers of downstream pathways activation) in order to evaluate the mechanisms of EGFR pathway activation in HNSCC and mechanisms of EGFR pathway inhibition by erlotinib hydrochloride in HNSCC tissue.

Evaluate post-erlotinib hydrochloride up-regulation of different receptors and molecules such as HER2 and 3, PDGFR, IGFR, mTOR, src, and aurora kinases, for which there are already specific inhibitors available for clinical studies.

Secondary

Evaluate the efficacy by overall response, safety, and tolerability of erlotinib hydrochloride before surgery in these patients.

Evaluate the role of FDG-PET scan as a predictor of response to erlotinib hydrochloride.

Evaluate the role of PET/CT in measuring the response to short-term treatment with erlotinib hydrochloride.

Evaluate incidence of risk factors for relapse in the surgical pathology specimens.

OUTLINE: Patients are grouped according to smoking status (non-actively smoking [not smoking, smoking an average of < 10 cigarettes daily, or smoking for < 1 year prior to enrollment] vs actively smoking [smoking an average of ≥ 10 cigarettes daily and smoking for ≥ 1 year]).

Patients undergo biopsies at baseline and after completion of study treatment. Tissue samples are analyzed by nano-liquid chromatography and mass spectrometry (nano-LC-MS/MS) for markers of activation and inhibition of different EGFR downstream pathways: PKC, c-Cbl, P-Erk, P- Akt, P-RAF, src, STAT3 and 5, cyclin D1, and D3, p21 and p27, c-fos, E-cadherin, vimentin, and correlative up-regulated receptors: Her 2, Her 3, Cox-2, IGF, VEGF, PDGFR, or other kinases such as src and aurora kinases A and B. The results are confirmed by western blot, protein array, and immunohistochemistry.

After completion of study treatment, patients are followed at 1 month.

History of interstitial lung disease (e.g., pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on chest CT scan

Clinically significant ophthalmologic abnormalities

HIV positivity

PRIOR CONCURRENT THERAPY:

More than 1 year since prior chemotherapy, biologic therapy, or hormonal therapy

No prior radiotherapy or chemotherapy for this tumor

No prior EGFR inhibitors

No concurrent grapefruit or grapefruit juice

No other concurrent investigational agents

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00601913

stage I squamous cell carcinoma of the oropharynx
stage II squamous cell carcinoma of the oropharynx
stage I squamous cell carcinoma of the larynx
stage II squamous cell carcinoma of the larynx
stage I squamous cell carcinoma of the lip and oral cavity
stage II squamous cell carcinoma of the lip and oral cavity

stage I squamous cell carcinoma of the hypopharynx
stage II squamous cell carcinoma of the hypopharynx
stage I verrucous carcinoma of the larynx
stage I verrucous carcinoma of the oral cavity
stage II verrucous carcinoma of the oral cavity